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BackgroundIn most industrialized societies, regulations, inspections, insurance, and legal options are established to support workers who suffer injury, disease, or death in relation to their work; in practice, these resources are imperfect or even unavailable due to workplace or employer obstruction. Thus, limitations exist to identify unmet needs in occupational safety and health information. ObjectiveThe aim of this study was to explore hidden issues related to occupational accidents by examining social network services (SNS) data using topic modeling. MethodsBased on the results of a Google search for the phrases occupational accident, industrial accident and occupational diseases, a total of 145 websites were selected. From among these websites, we collected 15,244 documents on queries related to occupational accidents between 2002 and 2018. To transform unstructured text into structure data, natural language processing of the Korean language was conducted. We performed the latent Dirichlet allocation (LDA) as a topic model using a Python library. A time-series linear regression analysis was also conducted to identify yearly trends for the given documents. ResultsThe results of the LDA model showed 14 topics with 3 themes: workers’ compensation benefits (Theme 1), illicit agreements with the employer (Theme 2), and fatal and non-fatal injuries and vulnerable workers (Theme 3). Theme 1 represented the largest cluster (52.2%) of the collected documents and included keywords related to workers’ compensation (ie, company, occupational injury, insurance, accident, approval, and compensation) and keywords describing specific compensation benefits such as medical expense benefits, temporary incapacity benefits, and disability benefits. In the yearly trend, Theme 1 gradually decreased; however, other themes showed an overall increasing pattern. Certain queries (ie, musculoskeletal system, critical care, and foreign workers) showed no significant variation in the number of queries. ConclusionsWe conducted LDA analysis of SNS data of occupational accident–related queries and discovered that the primary concerns of workers posting about occupational injuries and diseases were workers’ compensation benefits, fatal and non-fatal injuries, vulnerable workers, and illicit agreements with employers. While traditional systems focus mainly on quantitative monitoring of occupational accidents, qualitative aspects formulated by topic modeling from unstructured SNS queries may be valuable to address inequalities and improve occupational health and safety.

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed subgenome dominance remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

Abstract Background Diphtheria is a re-emerging infectious disease and public health concern worldwide and in Vietnam with increasing cases in recent years. This study aimed to assess the anti-diphtheria toxoid antibodies status in Khanh Hoa Province and identify factors contributing to the vaccination policy in the south-central coast of Vietnam. Methods This was a cross-sectional study to evaluate the seroprevalence of anti-diphtheria toxoid antibodies among 1,195 participants, aged 5 – 40 years in Khanh Hoa Province, Vietnam. Immunoglobulin G antibody levels against diphtheria were detected using a commercial anti-diphtheria toxoid enzyme-linked immunosorbent assay (SERION ELISA classic Diphtheria Immunoglobulin G) and were categorized following the World Health Organization guidelines. Results The mean anti-diphtheria toxoid antibody levels were 0.07 IU/ml (95% Confidence Interval: 0.07–0.08). Anti-diphtheria toxoid antibody levels were found to be associated with age and history of diphtheria vaccination. The 5–15 years age group had the highest levels (0.09 IU/ml), while the older age group had the lowest antibody level (p

Abstract Stacking two-dimensional (2D) van der Waals (vdW) materials in a layered bulk structure provides an appealing platform for the emergence of exotic physical properties. As a vdW crystal with exceptional plasticity, InSe offers the opportunity to explore various effects arising from the coupling of its peculiar mechanical behaviors and other physical properties. Here, we employ neutron scattering techniques to investigate the correlations of plastic interlayer slip, lattice anharmonicity, and thermal transport in InSe crystals. Not only are the interlayer slip direction and magnitude well captured by shifts in the Bragg reflections, but we also observe a deviation from the expected Debye behaviour in the heat capacity and lattice thermal conductivity. Combining the experimental data with first-principles calculations, we tentatively attribute the observed evidence of strong phonon-phonon interactions to a combination of a large acoustic-optical frequency resonance and a nesting effect. These findings correlate the macroscopic plastic slip and the microscopic lattice dynamics, providing insights into the mechano-thermo coupling and modulation in 2D vdW materials.

Abstract Background Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. Methods Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. Results Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. Conclusions Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors regulate plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption. This study investigated the impact of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic energy regulation. To directly investigate the role of SGLT2 inhibitors in the hypothalamus, we administered EMPA through intracerebroventricular (i.c.v.) injections into the murine ventricles. After dental cementing the i.c.v. cannula onto the skull, the mice were given 5 days to recover before receiving vehicle or EMPA (50 nM/2 μL) injections. In a high-fat diet (HFD)-induced obesity model, we determined the gene expression levels of agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates AgRP and POMC gene transcription in hypothalamic cell lines. We found that EMPA directly influenced the expression of endogenous mRNA of POMC and AgRP, which are critical for energy homeostasis, and modulated their transcription in high-fat diet-induced obese mice. Additionally, EMPA affected the expression of FoxO1, a key transcriptional regulator of glucose homeostasis, thereby regulating the transcriptional activity of POMC and AgRP. These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.

Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/β-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.

Introduction Withdrawal symptoms lead to smoking relapse and reduce the intention to quit. The present pilot RCT examined the effect of simple and very brief handgrip and isometric exercises on reducing withdrawal symptoms, measured by the strength of tobacco craving, Questionnaire of Smoking Urges-Brief (QSU-B), Mood and Physical Symptoms Scale (MPSS), and Positive and Negative Affect Schedule (PANAS). Methods In this 2-arm, open-labeled pilot RCT, 30 current smokers who had abstained from tobacco for at least 9 hours were randomly assigned (allocation ratio 1:1) to either the intervention group that watched a 5-minute video and did 5-minute handgrip and isometric exercises (pulling and pushing) or control group that watched 10-minute healthy-diet videos. Measurements were taken before, immediately after, and 10 minutes post-intervention. Outcomes were selfreported strength of tobacco craving, QSU-B, MPSS, and PANAS scores. The effect size for group-by-time interaction was assessed using Cohen’s f2 (small=0.02, medium=0.15, large=0.35). Results Group-by-time interactions showed that the intervention group showed larger reductions than the control group in the strength of tobacco craving (Cohen’s f2=0.54, 95% CI: 0.52–0.57), QSU-B (Cohen’s f2=0.77; 95% CI: 0.74–0.80), and MPSS (Cohen’s f2=0.51; 95% CI: 0.46–0.56) over the three measurement points. Conclusions This RCT showed that simple and brief handgrip and isometric exercises could immediately reduce withdrawal symptoms and up to 10 minutes. CLINICAL TRIAL REGISTRATION: in https://clinicaltrials.gov/ IDENTIFIER: NCT04059497

Abstract The global older adult population is increasing. Early detection and intervention through health check-ups are crucial for successful aging, as they play a significant role in identifying and addressing diseases. This study explored the relationship between the utilization of senior centers and the promotion of health check-ups. It utilized data from 10,097 individuals aged 65 years and above, sourced from the 2020 Elderly Survey in South Korea. The primary variable of interest was classified into two groups: those who utilized senior centers and those who did not. Subgroups were further categorized based on the frequency of usage and the presence of family members among senior centers users. Logistic regression analyses were conducted to assess the association between the utilization of senior centers and participation in health check-ups. Both men and women utilizing senior centers demonstrated a higher likelihood of participating in health check-ups compared with those who did not use senior centers. Participants visiting senior centers in a week exhibited a progressively higher likelihood of engaging in health check-ups compared with those who visited such senior centers zero times a week. Senior centers can serve as effective intervention methods to enhance health check-ups among older adults. Furthermore, this can contribute to fostering successful aging among older adults.

Abstract Intriguing “slidetronics” has been reported in van der Waals (vdW) layered non-centrosymmetric materials and newly-emerging artificially-tuned twisted moiré superlattices, but correlative experiments that spatially track the interlayer sliding dynamics at atomic-level remain elusive. Here, we address the decisive challenge to in-situ trace the atomic-level interlayer sliding and the induced polarization reversal in vdW-layered yttrium-doped γ-InSe, step by step and atom by atom. We directly observe the real-time interlayer sliding by a 1/3-unit cell along the armchair direction, corresponding to vertical polarization reversal. The sliding driven only by low energetic electron-beam illumination suggests rather low switching barriers. Additionally, we propose a new sliding mechanism that supports the observed reversal pathway, i.e., two bilayer units slide towards each other simultaneously. Our insights into the polarization reversal via the atomic-scale interlayer sliding provide a momentous initial progress for the ongoing and future research on sliding ferroelectrics towards non-volatile storages or ferroelectric field-effect transistors.

The bidirectional relationship between osteochondral defects (OCD) and osteoarthritis (OA), with each condition exacerbating the other, makes OCD regeneration in the presence of OA challenging. Type II collagen (Col2) is important in OCD regeneration and the management of OA, but its potential applications in cartilage tissue engineering are significantly limited. This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration. Furthermore, the repair potential of Col2 scaffolds was validated in over critical-sized OCD models. After 90 days or 150 days since scaffold implantation, complete healing was observed histologically in critical-sized OCD, evidenced by the excellent integration with surrounding native tissues. The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties. The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue. Additionally, transcriptome and proteome analysis revealed the hindrance of TGF-β-Smad1/5/8 in regenerated OA tissue. In conclusion, the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-β-Smad1/5/8 signaling pathway.

Abstract Seamounts are globally distributed across the oceans and form one of the major oceanic biomes. Here, we utilized combined analyses of bulk metagenome and virome to study viral communities in seamount sediments in the western Pacific Ocean. Phylogenetic analyses and the protein-sharing network demonstrate extensive diversity and previously unknown viral clades. Inference of virus-host linkages uncovers extensive interactions between viruses and dominant prokaryote lineages, and suggests that viruses play significant roles in carbon, sulfur, and nitrogen cycling by compensating or augmenting host metabolisms. Moreover, temperate viruses are predicted to be prevalent in seamount sediments, which tend to carry auxiliary metabolic genes for host survivability. Intriguingly, the geographical features of seamounts likely compromise the connectivity of viral communities and thus contribute to the high divergence of viral genetic spaces and populations across seamounts. Altogether, these findings provides knowledge essential for understanding the biogeography and ecological roles of viruses in globally widespread seamounts.

Abstract Background Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis. Materials and methods Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman’s correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test. Results Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1. Conclusions This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.

Sintered ore used as blast furnace burden materials is produced by mixing iron ore, coke, and limestone, then burning the coke and sintering the iron ore with the combustion heat. Among the coke charged, A particle size of 0.25 mm or less has an insignificant effect as a heat source and adhere to the surface of other materials to inhibit the reaction between oxygen and raw materials, thereby decreasing the quality of sintered ore. Therefore, to increase combustion efficiency, it is necessary to reduce the ratio of coke breeze in the charged coke. In this study, theoretical calculation, experiment and simulation were conducted to investigate the possibility of size classification by drag force in the process of dropping coke after being transported through a belt conveyor. The height of belt conveyor was at 1m, and velocity of the belt was 1.5, 2.3, and 2.6 m/s, which were considered as experimental variables. After falling, the distribution of coke particle size according to the horizontal travel distance was confirmed, and a fall trajectory prediction formula model was created through the drag model of polydisperse system and compared with the experimental and analysis results.

BackgroundThe relationships between alcohol marketing exposure, alcohol use, and purchase have been widely studied. However, prospective studies examining the causal relationships in real-world settings using mobile health tools are limited. ObjectiveWe used ecological momentary assessment (EMA) to examine both the within-person– and between-person–level effects of alcohol marketing exposure on any alcohol use, amount of alcohol use, any alcohol purchase, and frequency of alcohol purchase among university students. MethodsFrom January to June 2020, we conducted a prospective cohort study via EMA among university students in Hong Kong who reported current drinking. Over 14 consecutive days, each participant completed 5 fixed-interval, signal-contingent EMAs daily via a smartphone app. Each EMA asked about the number and types of alcohol marketing exposures, the amount and types of alcohol used, and whether any alcohol was purchased, all within the past 3 hours. We used 2-part models, including multilevel logistic regressions and multilevel gamma regressions, to examine if the number of alcohol marketing exposure was associated with subsequent alcohol use and alcohol purchase. ResultsA total of 49 students participated, with 33% (16/49) being male. The mean age was 22.6 (SD 2.6) years. They completed 2360 EMAs (completion rate: 2360/3430, 68.8%). Participants reported exposure to alcohol marketing in 5.9% (140/2360), alcohol use in 6.1% (145/2360), and alcohol purchase in 2.4% (56/2360) of all the EMAs. At the between-person level, exposure to more alcohol marketing predicted a higher likelihood of alcohol use (adjusted odd ratio [AOR]=3.51, 95% CI 1.29-9.54) and a higher likelihood of alcohol purchase (AOR=4.59, 95% CI 1.46-14.49) the following day. Exposure to more alcohol marketing did not increase the amount of alcohol use or frequency of alcohol purchases the following day in participants who used or purchased alcohol. At the within-person level, exposure to more alcohol marketing was not associated with a higher likelihood of alcohol use, amount of alcohol use, higher likelihood of alcohol purchase, or frequency of alcohol purchases the following day (all Ps>.05). Each additional exposure to alcohol marketing within 1 week predicted an increase of 0.85 alcoholic drinks consumed in the following week (adjusted B=0.85, 95% CI 0.09-1.61). On days of reporting alcohol use, the 3 measures for alcohol marketing receptivity were not associated with more alcohol use or purchase (all Ps>.05). ConclusionsBy using EMA, we provided the first evidence for the effect of alcohol marketing exposure on initiating alcohol use and purchase in current-drinking university students. Our findings provide evidence of the regulation of alcohol marketing for the reduction of alcohol use and purchase among young adults.

ABSTRACT: In poultry industry, the strategies for elevating of protein accretion with minimizing fat deposition have been applied, and seaweed algae has been focused one of the potential candidates. Accordingly, the purpose of this study was to investigate the effects of algae (Ascophllum Nodosum) extract (AE) on the growth performance and body composition of broiler chickens. A total of 240 one-day-old Ross 308 broiler chickens were allotted to 4 dietary treatment groups and fed experimental diets containing different concentrations of AE for 35 d as follows: 0 mg/kg (control, CON), 1,250 mg/kg (LAE), 2,500 mg/kg (MAE), or 5,000 mg/kg (HAE). At the end of the experiment, 40 chickens were sacrificed and samples of their blood, breast muscle, liver, and abdominal fat were collected and analyzed. Growth performance was improved in the LAE group compared to that in the CON (P < 0.05). The weight of abdominal fat was lower in the HAE group than in the CON group (P < 0.05). Serum triglyceride levels were also decreased in the HAE group compared to those in the CON and LAE groups (P < 0.05). Adipocytes were smaller in the HAE group than in all other treatments, and their size distribution was shifted more towards smaller adipocytes compared to those in the LAE group (P < 0.05). Relative mRNA levels in abdominal adipose tissue of fatty acid synthase and stearyl-CoA desaturase, which are involved in fatty acid synthesis, were all downregulated by supplementation with AE (P < 0.05). In addition, the protein levels of peroxisome proliferator-activated receptor gamma were decreased and the ratio of phosphorylated acetyl-CoA carboxylase to total ACC was increased, both of which indicate that lipogenesis was suppressed (P < 0.05). Hepatic transcript levels of sterol regulatory element-binding protein and its downstream enzymes fatty acid synthase and sterol-CoA desaturase were also lower in all AE treatments compared to those in the CON group (P < 0.05). These results indicate that the seaweed algae (Ascophllum Nodosum) extract reduces fat accumulation in both adipose tissue and the liver by modulating lipogenesis.

Abstract Aloperine (ALO), a quinolizidine‐type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non‐small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome‐1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO‐induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti‐PD‐L1/TGF‐β bispecific antibody in inhibiting LLC‐derived subcutaneous tumor models. Thus, ALO is first identified as a novel late‐stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.

Abstract Background Gastric cancer (GC), particularly for advanced stage of GC, commonly undergoes peritoneal metastasis (PM), which is the leading cause of GC‐related death. However, there currently has no reliable biomarker to predict the onset of GCPM. It is well known that the imbalance of gut microbiota contributes to the development and metastasis of gastrointestinal tumors. Unfortunately, little is known about how the alternation in gut microbiota is associated with the onset of GCPM. Methods Our current study analyzed structural characteristics and functional prediction of gut microbiota in GC patients with PM (PM group) and without PM (non‐PM group). Fresh fecal samples were collected from a discovery cohort (PM = 38, non‐PM = 54) and a validation cohort (PM = 15, non‐PM = 21) of GC patients and their 16S ribosomal RNA (16s rRNA) gene amplicons were sequenced, followed by bioinformatics. Results The results indicated an increase in the biodiversity of gut microbiota in the non‐PM group of the discovery cohort, compared with the PM group. Moreover, LEfSe analysis found 31 significantly different microorganisms, of which the Roseburia ranked the fifth in the random forest (RF) model. The characteristics of intestinal microbiota in GCPM patients were changed, and the abundance of Roseburia in gut microbiota from the GCPM patients was reduced and receiver operating characteristic (ROC) analysis revealed that the reduced abundance of gut Roseburia effectively predicted the onset of GCPM. Conclusion This signature was also observed in the validation cohort. Therefore, Roseburia is a protective microbial marker and the reduced abundance of Roseburia in gut microbiota may help early diagnosis of GCPM.

Photo modulated optical reflectance (PMOR) is an ideal ultra-shallow junction area metrology technique for measurement of transistor dopant distribution in integrated circuit fabrication, and the characterization of process parameters such as implant energy, implant angle, and implant dose has a significant impact on the accuracy of the ion implantation process. This study utilized deep learning to analyze various process parameters concurrently and assessed its performance on boron-doped silicon samples, the data were obtained from the power curves measured from Carrier Illumination (CI) experiments in PMOR, a deep learning model with multi-task learning architecture was developed and trained to characterize multiple process parameters, and the PMOR model incorporating a multi-task learning architecture for process parameters demonstrated superior performance in terms of accuracy and speed of characterization. The analyses indicated that applying deep learning methods to CI metrology in PMOR technology is feasible. In particular, compared with the conventional carrier irradiation technique, the ability to obtain the implantation dose and doping profile along with other process parameters such as implantation energy, implantation angle, and implantation type can better assist in the accurate realization of the ion implantation process with acceptable accuracy and time cost. [ABSTRACT FROM AUTHOR]

Upregulation of the nutritional value of feed is the major target of various studies in the livestock industry, and dietary enzyme supplementation could aid in digesting the nondegrading nutrients of grains in feed ingredients. Dried distillers’ grains with solubles (DDGS) is a byproduct of the fermentation process in the beverage industry and can be used as a large supply source of fiber in feed. Therefore, we conducted an experiment with male broiler chickens to investigate the effect of various types of enzymes on DDGS and compare the efficacy of single enzyme and multienzyme complexes on growth performance and gut environments in broiler chickens. We used 420 1-day-old broiler chickens (Ross 308), and they were allotted into 4 dietary treatments with seven replications (CON, corn-soybean meal [SBM] diet; NC, DDGS supplemented diet; SE, 0.05 % of mannanase supplemented DDGS-based diet; MC, 0.10% of multienzyme complex (mannanase and xylanase, glucanase) supplemented DDGS-based diet. The dietary exogenous enzyme in the DDGS-supplemented diet could improve growth performance as much as the growth of the control group, and digestibility of dry matter, crude protein, and gross energy were significantly increased by enzyme addition in groups of chicks fed DDGS-supplementation diet. Moreover, the populations of pathogenic bacteria, coliforms, and Bacteroidetes were significantly decreased by enzyme supplementation, which might lead to improved gut mucus-secreting cells and inflammatory cytokines in the jejunum. Collectively, dietary single enzyme and multienzyme complexes could improve gut environments, including intestinal immune responses and gut microbial population, and lead to improvement of growth performance in broiler chickens.

Abstract There is a substantial rise in the global incidence of obesity. Brown rice contains metabolic substances that can help minimize the prevalence of obesity. This study evaluated nine brown rice varieties using probiotic fermentation using Pediococcus acidilacti MNL5 to enhance bioactive metabolites and their efficacy. Among the nine varieties, FBR-1741 had the highest pancreatic lipase inhibitory efficacy (87.6 ± 1.51%), DPPH assay (358.5 ± 2.80 mg Trolox equiv./100 g, DW), and ABTS assay (362.5 ± 2.32 mg Trolox equiv./100 g, DW). Compared to other fermented brown rice and FBR-1741 varieties, UHPLC-Q-TOF-MS/MS demonstrated significant untargeted metabolite alterations. The 17 most abundant polyphenolic metabolites in the FBR-1741 variety and 132 putative targets were assessed for obesity-related target proteins, and protein interaction networks were constructed using the Cystoscope software. Network pharmacology analysis validated FBR-1741 with active metabolites in the C. elegans obesity-induced model. Administration of FBR-1741 with ferulic acid improved lifespan decreased triglycerides, and suppressed the expression of fat-related genes. The enhanced anti-obesity properties of FBR-1741 suggest its implementation in obesity-functional food.

Abstract Background The reduced treatment time of dental implants with immediate loading protocol is an appealing solution for dentists and patients. However, there remains a significant risk of early peri-implant bone response following the placement of immediately loaded implants, and limited information is available regarding loading directions and the associated in vivo characteristics of peri-implant bone during the early stages. This study aimed to investigate the effects of immediate loading directionality on the expression of mechanical sensing protein PIEZO1 and the healing process of peri-implant bone in the early stage. Methods Thirty-two implants were inserted into the goat iliac crest models with 10 N static lateral immediate loading applied, followed by histological, histomorphological, immunohistochemical, X-ray microscopy and energy dispersive X-ray spectroscopy evaluations conducted after 10 days. Results From evaluations at the cellular, tissue, and organ levels, it was observed that the expression of mechanical sensing protein PIEZO1 in peri-implant bone was significantly higher in the compressive side compared to the tensile side. This finding coincided with trends observed in interfacial bone extracellular matrix (ECM) contact percentage, bone mass, and new bone formation. Conclusions This study provides a novel insight into the immediate loading directionality as a potential influence factor for dental implant treatments by demonstrating differential effects on the mechanical sensing protein PIEZO1 expression and related early-stage healing processes of peri-implant bone. Immediate loading directions serve as potential therapeutic influence factors for peri-implant bone during its early healing stage.

Abstract Background The poultry industry encounters a number of factors that affect growth performance and productivity; nutrition is essential for sustaining physiological status and protecting against stressors such as heat, density, and disease. The addition of vitamins, minerals, and amino acids to the diet can help restore productivity and support the body’s defense mechanisms against stress. Methionine (Met) is indispensable for poultry’s energy metabolism, physiology, performance, and feed utilization capacity. Through this study, we aimed to examine the physiological effects of methionine supplementation on poultry as well as alterations of intestinal microbiome. Methods We utilized the DL- and L- form of methionine on Caenorhabditis elegans and the FIMM (Fermentor for intestine microbiota model) in-vitro digesting system. A genomic-analysis of the transcriptome confirmed that methionine supplementation can modulate growth-related physiological metabolic pathways and immune responses in the host poultry. The C. elegans model was used to assess the general health benefits of a methionine supplement for the host. Results Regardless of the type or concentration of methionine, supplementation with methionine significantly increased the lifespan of C. elegans. Feed grade L-Methionine 95%, exhibited the highest lifespan performance in C. elegans. Methionine supplementation increased the expression of tight junction genes in the primary intestinal cells of both broiler and laying hens, which is directly related to immunity. Feed grade L-Methionine 95% performed similarly or even better than DL-Methionine or L-Methionine treatments with upper doses in terms of enhancing intestinal integrity. In vitro microbial cultures of healthy broilers and laying hens fed methionine revealed changes in intestinal microflora, including increased Clostridium, Bacteroides, and Oscillospira compositions. When laying hens were given feed grade L-Methionine 95% and 100%, pathogenic Campylobacter at the genus level was decreased, while commensal bacteria were increased. Conclusions Supplementation of feed grade L-Methionine, particularly L-Methionine 95%, was more beneficial to the host poultry than supplementing other source of methionine for maintaining intestinal integrity and healthy microbiome.

Abstract Background Entirely impacted mandibular third molar (EIM3M) concerns the pathological external root resorption (ERR) of the adjacent mandibular second molar (M2M) and formation of granulation tissue between two molars. The study aimed to clarify the effect of αENaC, a mechano-sensitive molecule, to explore the mechanical mechanism in this scenario. Methods The force EIM3M exerted on M2M was proved by finite element analysis. αENaC expressions were tested by real-time polymerase chain reaction (PCR), immunoblotting and immunofluorescence. Inflammatory and epithelial-mesenchymal transition (EMT)-related molecules expressions were also detected by real-time PCR. The correlation was analyzed by Spearman’s correlation analysis, and receiver-operator characteristic (ROC) curve was further exhibited. Results The force was concentrated in the ERR area. αENaC was upregulated, positively correlated with ERR degree and localized to the fibroblasts in ERR granulation tissues. Moreover, αENaC was respectively and positively associated with elevated TNF-α and N-cadherin in ERR granulation tissues. More importantly, ROC analysis verified αENaC as a novel indication of the incidence of this disease. Conclusions Our finding revealed the force from EIM3M causing ERR of M2M, and elucidated the expression and localization of αENaC and its positive correlation with inflammation, EMT and disease severity, suggesting a novel indication in this disease.

Abstract Quantum effects in photosynthetic energy transport in nature, especially for the typical Fenna-Matthews-Olson (FMO) complexes, are extensively studied in quantum biology. Such energy transport processes can be investigated as open quantum systems that blend the quantum coherence and environmental noise, and have been experimentally simulated on a few quantum devices. However, the existing experiments always lack a solid quantum simulation for the FMO energy transport due to their constraints to map a variety of issues in actual FMO complexes that have rich biological meanings. Here we successfully map the full coupling profile of the seven-site FMO structure by comprehensive characterisation and precise control of the evanescent coupling of the three-dimensional waveguide array. By applying a stochastic dynamical modulation on each waveguide, we introduce the base site energy and the dephasing term in coloured noise to faithfully simulate the power spectral density of the FMO complexes. We show our photonic model well interprets the phenomena including reorganisation energy, vibrational assistance, exciton transfer and energy localisation. We further experimentally demonstrate the existence of an optimal transport efficiency at certain dephasing strength, providing a window to closely investigate environment-assisted quantum transport.

Introduction: Viruses are abundant and ecologically significant in marine ecosystems. However, the virome of deep-sea sediments is not extensively investigated. Objectives: To explore the distribution pattern of deep-sea viruses on a global scale, the viromes of DNA viruses isolated from 138 sediments of 5 deep-sea ecosystems were characterized. Methods: The viral particles were purified from each sediment sample. Then the viral DNAs were extracted and subjected to viral metagenomic analysis. Results: Here, we constructed a global deep-sea environmental virome dataset by analyzing the viral DNA of 138 sediment samples. A total of 347,737 viral operational taxonomic units (vOTUs) were identified, of which 84.94% were hitherto unknown, indicating that deep sea was a reservoir of novel DNA viruses. Furthermore, circular viral genome analysis revealed 98,581 complete genomes. The classified vOTUs included eukaryotic (44.55%) and prokaryotic (25.75%) viruses, and were taxonomically assigned to 63 viral families. The composition and abundance of the deep-sea sediment viromes were dependent on the deep-sea ecosystem as opposed to geographical region. Further analysis revealed that the viral community differentiation in different deep-sea ecosystems was driven by the virus-mediated energy metabolism. Conclusion: Our findings showed that deep-sea ecosystems are a reservoir of novel DNA viruses and the viral community is shaped by the environmental characteristics of deep-sea ecosystems, thus presenting critical information for determining the ecological significance of viruses in global deep-sea ecosystems.

Abstract The ground state search of the Ising model can be used to solve many combinatorial optimization problems. Under the current computer architecture, an Ising ground state search algorithm suitable for hardware computing is necessary for solving practical problems. Inspired by the potential energy conversion of the springs, we propose the Spring-Ising Algorithm, a point convolutional neural network algorithm for ground state search based on the spring vibration model. Spring-Ising Algorithm regards the spin as a moving mass point connected to a spring and establishes the equation of motion for all spins. Spring-Ising Algorithm can be mapped on AI chips through the basic structure of the neural network for fast and efficient parallel computing. The algorithm has shown promising results in solving the Ising model and has been tested in the recognized test benchmark K2000. The optimal results of this algorithm after 10,000 steps of iteration are 2.9% of all results. The algorithm introduces the concept of dynamic equilibrium to achieve a more detailed local search by dynamically adjusting the weight of the Ising model in the spring oscillation model. Spring-Ising Algorithm offers the possibility to calculate the Ising model on a chip which focuses on accelerating neural network calculations.

Abstract Reinforcement learning (RL) stands as one of the three fundamental paradigms within machine learning and has made a substantial leap to build general-purpose learning systems. However, using traditional electrical computers to simulate agent-environment interactions in RL models consumes tremendous computing resources, posing a significant challenge to the efficiency of RL. Here, we propose a universal framework that utilizes a photonic integrated circuit (PIC) to simulate the interactions in RL for improving the algorithm efficiency. High parallelism and precision on-chip optical interaction calculations are implemented with the assistance of link calibration in the hybrid architecture PIC. By introducing similarity information into the reward function of the RL model, PIC-RL successfully accomplishes perovskite materials synthesis task within a 3472-dimensional state space, resulting in a notable 56% improvement in efficiency. Our results validate the effectiveness of simulating RL algorithm interactions on the PIC platform, highlighting its potential to boost computing power in large-scale and sophisticated RL tasks.

Abstract DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome DNA damage, we investigate how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting Interleukin enhancer binding factor 2 (ILF2), a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo adaptive metabolic rewiring to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identify the mitochondrial DNA repair protein DNA2, whose loss of function suppresses MM cells’ ability to overcome ILF2 ASO−induced DNA damage, as being essential to counteracting oxidative DNA damage. Our study reveals a mechanism of vulnerability of MM cells that have an increased demand for mitochondrial metabolism upon DNA damage activation.

Introduction: Viruses are the most abundant and diverse life forms on the earth. Both DNA viruses and RNA viruses play important roles in marine ecosystems via regulating biogeochemical cycles. Objectives: However, the virome of marine RNA viruses has been rarely explored so far. In this study, therefore, the environmental viromes of deep-sea sediment RNA viruses were characterized on a global scale to reveal the global virosphere of deep-sea RNA viruses. Methods: The viral particles were purified from each of 133 deep-sea sediment samples and then characterized based on metagenomes of RNA viruses. Results: In this study, we established the global virome dataset of deep-sea RNA viruses purified from 133 sediment samples that were collected from typical deep-sea ecosystems of three oceans. A total of 85,059 viral operational taxonomic units (vOTUs) were identified, of which only 1.72% were hitherto known, indicating that the deep-sea sediment is a repository of novel RNA viruses. These vOTUs were classified into 20 viral families, including prokaryotic (7.09%) and eukaryotic (65.81%) RNA viruses. Furthermore, 1,463 deep-sea RNA viruses with complete genomes were obtained. The differentiation of RNA viral communities was driven by the deep-sea ecosystems as opposed to geographical region. Specifically, the virus-encoded metabolic genes took great effects on the differentiation of RNA viral communities by mediating the energy metabolism in the deep-sea ecosystems. Conclusions: Therefore, our findings indicate that the deep sea is a vast reservoir of novel RNA viruses for the first time, and the differentiation of RNA viral communities is driven by the deep-sea ecosystems through energy metabolism.

Abstract Background Right-side aortic arch concomitant with Kommerell’s diverticulum (KD) is a rare and complex ailment, and there is no consensus on the optimal strategy to deal with this congenital anomaly. We retrospectively analyzed and summary of the cases treated in our center with individual treatment methods for different situations. Methods Between September 2018 and December 2021, 10 patients experienced surgical therapy at our institution who presented with a Kommerell’s diverticulum arising from an aberrant subclavian artery from the right-side aortic arch. Four main surgical techniques were applied to those patients: 1. total arch replacement with frozen elephant trunk implantation (n = 2); 2. hybrid procedure combining open arch repair and endovascular intervention (n = 1); 3. total endovascular repair using thoracic endovascular aortic repair (TEVAR) with or without left subclavian artery (LSCA) revascularization (n = 6); 4. direct repair underwent endoaneurysmorrhaphy. Clinical characteristics and outcomes were collected. Results The mean age of these 10 patients was 56.5 years (range 29–79 years) and only 1 woman. The pathology includes aortic dissection (n = 6) and aneurysm (n = 4). The mean diverticulum size was 41.4 [24.2–56.8] mm. There were no in-hospital deaths, and the median hospital stay was 22 [15–43] days. During the follow-up period (21.4 months, 1–44 months), one died of an unknown cause and one died of esophageal fistula. Two patients underwent second-stage endovascular intervention for distal lesion. And none of the patients had endoleak during the follow-up period. Conclusions Each of the procedures we have mentioned here has its advantages and disadvantages; individualized treatment should meet the appropriate indications. A single-branched stent graft is feasible and effective in the treatment of aortic disease combined with Kommerell’s diverticulum.

Abstract Internet use disorder (IUD) is an emerging social and mental health concern. This study aimed to analyze the relative risk of IUD in late childhood among children whose mothers experienced peripartum depressive symptoms. This study included 762 participants (397 boys and 365 girls) and was conducted in 2017 (aged 9) and 2019 (aged 11). We analyzed the adjusted relative risk of being at high risk for IUD based on whether the mother experienced depressive symptoms during pregnancy or one month after delivery. We also considered the persistence of depressed mood for 4 months after delivery and the severity of peripartum depressive symptoms. From 2017, 20.7% of boys and 14.0% of girls were at high risk of developing IUD. Compared to the non-peripartum depressive group, girls whose mothers experienced peripartum depressive symptoms and those that persisted for 4 months were 1.084 and 1.124 times more likely to be at high risk of IUD (95% confidence interval = 1.005–1.170 and 1.013–1.248), respectively. There were no statistically significant differences among boys. Peripartum depressed mood could be one of risk factors of IUD. IUD needs to be monitored in children whose mothers experienced peripartum depressive symptoms.